Cellular/Mobile Phone Use and Intracranial Tumours September 2008
This document was produced by the National Collaborating Centre for Environmental Health at the BC Centre for Disease Control with funding from the Public Health Agency of Canada, September 2008. Permission is granted to reproduce this document in whole, but not in part. Photo credits: Aquacolor; licensed through istockphoto National Collaborating Centre for Environmental Health 400 East Tower 555 W 12 th Avenue Vancouver, BC V5Z 3X7 Tel: 604-707-2445 Fax: 604-707-2444 contact@ncceh.ca www.ncceh.ca Production of this report has been made possible through a financial contribution from the Public Health Agency of Canada. The views expressed herein do not necessarily represent the views of the Public Health Agency of Canada. ISBN: 978-0-9784317-8-5 National Collaborating Centre for Environmental Health 2008 September 2008 Cellular/Mobile Phone Use and Intracranial Tumours 2
Background Cell phone use is increasingly prevalent in Canada. Public concerns of a potential associated risk with have been raised. Further, recent media attention has focused on disparate precautionary policies implemented across jurisdictions in Canada and world-wide. In light of this and emerging epidemiological evidence, we review what is known about cell phone use and. Intracranial In 2008, the Canadian standardized incidence rate for brain cancer is estimated to be 8 per 100,000 for males and 6 per 100,000 for females. These rates have not increased compared to 1980 levels; in fact among females a decline in incidence of 3.6% per year since 2000 has been observed 1. Three types of are discussed in this review. Glioma is a malignant tumour with a high case fatality rate; acoustic and meningioma are benign and can usuy be treated with early diagnosis. Meta-analyses Three meta-analyses published since and two pooled INTERPHONE studies were reviewed (Tables 1 and 2). These studies pertain to in adults only. All three meta-analyses used a random effects model, which does not assume homogeneity of effects across the studies being pooled; however, Lahkola et al () also used a fixed effect model (assumes homogeneity) for selected analyses 2. Hardell et al (2008) provided little information on the methods used while Kan et al (2008) and Lahkola et al () examined heterogeneity between studies, conducted sensitivity analyses and tested for publication bias; none was identified 3,4,2. The two most recent meta-analyses (Hardell et al 2008, Kan et al 2008) were restricted to case-control studies and are based on the same set of articles with more recent publications added to Hardell et al 3,4. The sole exception is the exclusion of Muscat et al (2000) by Hardell et al (2008) with the rationale that results were not presented separately for glioma, acoustic and meningioma 3. Lahkola et al () included several additional older studies; Johansen et al (2001), a Danish cohort study, and three studies by Hardell et al 2. The latter were presumably not included in the other meta-analyses due to methodological considerations; these studies have been criticized for biases in participant recruiting, exposure assessment and unclear reporting. Summary of meta-analysis results Meta-analyses based on 10 years duration of use have detected a slightly increased risk (OR: 1.25, 95%CI: 1.01-1.54) for (Kan et al 2008) 4. Pooled analyses using shorter duration did not indicate an association (Lahkola et al ) 2. Restricting the analyses to 10 years and ipsilateral use (cell phone use on the same side as the tumour), the risk increased and was significantly associated for glioma (OR: 2.0, 95%CI: 1.2-3.4) and acoustic (OR: 2.4, 95%CI: 1.1-5.3, but not for meningioma (OR: 1.7, 95%CI: 0.99-3.1) (Hardell et al 2008) 3. Interpretation of results There is insufficient evidence to indicate a causal association. The evidence is most suggestive for ipsilateral occurring with ten or more years of use. Associations were only observed for regular cell phone use of 10 years. This exposure duration/latency is appropriate for cancer studies. Previous negative studies may have failed to detect an effect due to an insufficient duration of exposure or latency period. The number of study subjects for which these exposure metrics are available is relatively sm. September 2008 Cellular/Mobile Phone Use and Intracranial Tumours 3
Type of phone (analogue/digital) may influence this association. Earlier models (analogue phones) were likely used by long-term cell phone users. These phones emit greater radiation and may be associated with an increased risk of tumour development than the newer digital phones. Individual studies have examined the odds of using analogue phones but collectively no increased risk has been observed (Kan et al 2008, Lahkola et al ) 4,2. Years of exposure is just one exposure metric; the two most recent meta-analyses did not explore other indices of exposure, e.g., hours of cumulative use and cumulative number of cs, although this information has been reported in individual studies. The observed strengthening of the odds with 10 years and ipsilateral use increases the biological plausibility of the association; this suggests that the greatest risk is on the most exposed side of the brain. Results may indicate a true increase in risk with cell phone use; however, they may also indicate rec bias. Cases may have disproportionately reced ipsilateral cell phone use if they believed it to be related to the development of the tumour; this is plausible given media attention to the issue. If true, this would inflate the calculated risk. This appears to have occurred in some individual studies where ipsilateral use significantly increases the risk whereas contralateral use provides a protective effect suggesting information bias (Hepworth et al ) 5. Other methodological constraints involving individual studies included in the meta-analysis may have influenced the over results. For example, the use of proxy respondents, for deceased or very ill cases, may have introduced misclassification or bias in exposure assessment. This is of particular concern for glioma where there is a high case fatality proportion. Given the low and stable/declining Canadian brain cancer incidence rates, any increased risk attributable to cell phone use is very sm. Existing research is limited to adults; little is known about potential risks to children. A large cohort study is underway to examine potential risks in this population group (Feyching ) 6. Summary There is insufficient evidence to indicate a causal association between cell phone use and. There is weak evidence supporting an increase in odds of glioma, acoustic, and meningioma in adults with regular, ipsilateral use for 10 years or longer. Existing findings are suggestive but preliminary because they are based on few studies with sm numbers and potential biases. References 1. Canadian Cancer Society. Canadian Cancer Statistics [cited 2008]; Available from: URL:http://www.cancer.ca/vgn/images/portal/cit_86751114/10/34/614137951cw_library_WYNTK_Bladd er_punjabi.pdf 2. Lahkola A, Tokola K, Auvinen A. Meta-analysis of long-term mobile phone use and. Scand J Work Environ Health ;32(3):171-177. 3. Hardell L, Carlberg M, Söderqvist F, Mild KH. Meta-analysis of long-term mobile phone use and the association with brain. Int J Oncol 2008;32:1097-1103. 4. Kan P, Simonsen SE, Lyon JL, Kestle JRW. Cellular phone use and brain tumour: a meta-anaylsis. J Neurooncol. 2008;86:71-78. 5. Hepworth SJ, Schoemaker MJ, Muir KR, Swerdlow AJ, van Tongerren MJA, McKinney PA. Mobile phone use and risk of glioma in adults: case-control study. BMJ ;doi:10.1136/bmj.38720.687975.55. 6. Feychting M. CEFALO-A case-control study of brain in children and adolescents and mobile phone use. Epi ;17(6)S74. 7. Lahkola A, Auvinen A, Raitanen J, Schoemaker MJ, HC, Feychting M et al. Mobile phone use and risk of glioma in five North European countries. Int J Cancer 2007;120:1769-1775. 8. Schoemaker MJ, Swerdlow AJ, Ahlbom A, Auvinen A, Blaasaas KG, Cardis E et al. Mobile phone use and risk of acoustic : results of the interphone case-control study in five North European countries. Br J Cancer ;93:842-848. September 2008 Cellular/Mobile Phone Use and Intracranial Tumours 4
Appendix 1: Summary of Meta-Analyses of Cellular Phone Use and Intracranial Tumours Description of Meta-Analysis Results of Meta-Analysis Hardell et al. 2008 Kan et al. 2008 Studies included in Meta- Analysis Schlehofer et al. 2007 Klaeboe et al. 2007 Hours et al. 2007 Lahkola et al. 2007 Takebayashi et al. 2000 Schuz et al. Hepworth et al. Schoemaker et al. Auvinen et al. 2002 Inskip et al. 2001 Schuz et al. * Hepworth et al. * * * Schoemaker Auvinen et al. 2002 Inskip et al. 2001 Muscat et al. 2000 Design All case - control studies All casecontrol studies 5259/ 12074 Period n/s 2000- Tumour Type Exposure (years) Digital/ Analog Ipsilateral Odds Ratio (95% CI) glioma All n/s n/s 0.9(0.8-1.1) glioma 10 n/s n/s 338 / 511 1.2(0.8-1.9) glioma 10 n/s ipsilateral >133/>163 2.0(1.2-3.4) glioma 10 n/s contralateral >104/>175 1.1(0.6-2.0) acoustic All n/s n/s 824/4261 0.9(0.7-1.1) acoustic 10 n/s n/s 83/355 1.3(0.6-2.8) acoustic 10 n/s ipsilateral 53/167 2.4(1.1-5.3) acoustic 10 n/s contralateral 30/151 1.2(0.7-2.2) meningioma All n/s n/s 870/2,331 0.8(0.7-0.99) meningioma 10 n/s n/s 61/152 1.3(0.9-1.8) meningioma 10 n/s ipsilateral 20/46 1.7(0.99-3.1) meningioma 10 n/s contralateral 15/52 1.0(0.3-3.1) high-grade glioma low-grade glioma acoustic n/s n/s n/s 10 studies 0.90(0.81-0.99) 10 n/s n/s 5 studies 1.25(1.01-1.54) n/s digital n/s 0.86(0.68-1.09) n/s analog n/s 1.13(0.83-1.54) n/s n/s n/s 5 studies 0.86(0.70-1.05) n/s n/s n/s 1.14(0.91-1.43) n/s n/s n/s 3 studies 0.96(0.83.10) meningioma n/s n/s n/s 5 studies 0.64(0.56-0.74 September 2008 Cellular/Mobile Phone Use and Intracranial Tumours 5
Description of Meta-Analysis Results of Meta-Analysis Lahkola et al. Studies included in Meta- Analysis Shoemaker Muscat et al. 2002 2002 Auvinen et al. 2002 Johansen et al. 2001 Inskip et al. 2001 Muscat et al. 2000 1999 Design 11 casecontrol studies and one cohort study 2780 cases Period 1966 - Tumour Type Exposure (years) ever to >5 yrs glioma ever to >5 yrs acoustic ever to >5 yrs meningiomas ever to >5 yrs Digital/ Analog Ipsilateral Odds Ratio (95% CI) n/s n/s 12 studies 0.98(0.83-1.16) >1 yr n/s ipsilateral 8 studies 1.36(0.99-1.87) >1 yr n/s contralateral 5 studies 1.02(0.78-1.35) n/s n/s 9 studies 0.96(0.78-1.18) n/s n/s 6 studies 1.07(0.89-1.30) n/s n/s 8 studies 0.87(0.72-1.05) Appendix 2: Pooled Interphone Studies Description of Pooled Analysis Results of Pooled Analysis Lahkola et al. 2007 Shoemaker et al. Country Denmark Finland Norway Sweden England Denmark Finland Norway Sweden England 1,521/ 3,301 Period 2000-678/3553 1999- Age 18-69 18-69 Tumour Type glioma acoustic Exposure Definition Cases / Odds Ratio (95% CI) Regular use 867/1853 0.78(0.68-0.91) since first use, 67/121 0.98(0.71,1.37) contralateral since first use, 77/117 1.39(1.01-1.92) ipsilateral Regular use 0.9(0.7-1.1) lifetime use, 0.9(0.5-1.8) contralateral lifetime use, 1.8(1.1-3.1) ipsilateral Comments Increasing trend with years since first use on ipsilateral side (p=0.04) No association reported with increasing number years of use (p=0.7) September 2008 Cellular/Mobile Phone Use and Intracranial Tumours 6
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